transcriptional repressor CTCF; 11-zinc finger protein; CCCTC-binding factor; CTCFL paralog (CTCF)

Function: - chromatin binding factor - binds to DNA sequence specific sites - role in transcriptional regulation by binding to chromatin insulators & preventing interaction between promoter & nearby enhancers & silencers - acts as transcriptional repressor binding to promoters of vertebrate MYC gene & BAG1 gene - also binds to the PLK & PIM1 promoters - acts as a transcriptional activator of APP - regulates APOA1/C3/A4/A5 gene cluster & controls MHC class II gene expression - role in oocyte & preimplantation embryo development by activating or repressing transcription - seems to act as tumor suppressor - role in the epigenetic regulation - participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus - on the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2 - role in gene silencing over considerable distances in the genome - preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation & maintaining methylation-free zones - inversely, binding to target sites is prevented by CpG methylation - role in chromatin remodeling - can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping - mediates interchromosomal association between IGF2/H19 & WSB1/NF1 & may direct distant DNA segments to a common transcription factory - causes local loss of histone acetylation & gain of histone methylation in the beta-globin locus, without affecting transcription - when bound to chromatin, it provides an anchor point for nucleosome positioning - seems to be essential for homologous X-chromosome pairing - may participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation - may play a role in preventing the propagation of stable methylation at the escape genes from X-inactivation - involved in sister chromatid cohesion - associates with both centromeres & chromosomal arms during metaphase & required for cohesin localization to CTCF sites - regulates asynchronous replication of IGF2/H19 - sumoylated on Lys-74 & Lys-689 - sumoylation of CTCF contributes to the repressive function of CTCF on the MYC P2 promoter (putative) - interacts with CHD8 Structure: - the 11 Zn⁺² fingers are highly conserved among vertebrates, exhibiting almost identical amino acid sequences - different subsets or combination of individual Zn⁺² fingers gives the ability to CTCF to recognize multiple DNA target sites - belongs to the CTCF Zn⁺²-finger protein family - contains 11 C2H2-type Zn⁺² fingers Compartment: - nucleus, nucleoplasm - chromosome, centromere - may translocate to the nucleolus upon cell differentiation - associates with both centromeres & chromosomal arms during metaphase - associates with the H19 ICR in mitotic chromosomes - may be preferentially excluded from heterochromatin during interphase Expression: - ubiquitous - absent in primary spermatocytes

General

C2H2 type zinc finger protein phosphoprotein transcriptional silencer (transcriptional repressor)

Properties

SIZE: entity length = 727 aa MW = 83 kD COMPARTMENT: cell nucleus MOTIF: Zn finger C2H2-type SITE: 266-288 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 294-316 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 322-345 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 351-373 EFFECTOR-BOUND: Zn+2 Thr phosphorylation site {T374} Zn finger C2H2-type SITE: 379-401 EFFECTOR-BOUND: Zn+2 Ser phosphorylation site {S402} Zn finger C2H2-type SITE: 407-430 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 437-460 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 467-489 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 495-517 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 523-546 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 555-577 EFFECTOR-BOUND: Zn+2 Ser phosphorylation site {S609} Ser phosphorylation site {S610} Ser phosphorylation site {S612}

Database Correlations

OMIM 604167 UniProt P49711 Pfam PF00096 Entrez Gene 10664 Kegg hsa:10664

References

UniProt :accession P49711